Healthy adult volunteers were inoculated intranasally with human parvovirus obtained from an asymptomatic blood donor. One week after inoculation, intense viremia was observed in seronegative volunteers, accompanied by a mild illness with pyrexia, malaise, myalgia, itching, and excretion of virus from the respiratory tract. In the following week hematologic studies revealed reticulocytopenia with an associated slight drop in hemoglobin concentration, lymphopenia, neutropenia, and a drop in platelet counts. At 17-18 days after inoculation a second-phase illness with rash and arthralgia lasting three to four days occurred in three of four infected volunteers. This study confirms the etiologic role of human parvovirus in erythematous rash illness, with the second-phase illness being consistent with adult cases of erythema infectiosum. Moreover, the hematologic changes associated with infection support the hypothesis that the same virus is responsible for the temporary arrest of erythropoiesis that leads to aplastic crisis in persons with chronic hemolytic anemia.

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SUMMARY The incidence of antecedent events and serological evidence of preceding infection were studied in 100 patients with acute idiopathic neuropathy and age and sex matched control subjects in South-East England. Symptoms of respiratory infections occurred within one month before onset of neuropathic symptoms in 38% of patients and 12% of controls (p < 0 001) and symptoms of gastrointestinal infections in 17% of patients and 3% of controls (p < 0-005). Immunisations, insect bites and animal contact were equally common in the patient and control subjects. Eight per cent of patients had undergone an operation within the preceding 3 months. Six per cent of patients had co-existing "autoimmune" diseases. Serological evidence of recent infection was identified in 31% of patients. Campylobacter jejuni (14%) and cytomegalovirus (11%) were both significantly more frequently demonstrated in patients than controls. Serological evidence of recent infection with mycoplasma (1%), Epstein Barr virus (1-2%) and parvovirus B19 (4%) was also identified in the patients but not more frequently than in the controls. Possible explanations for the association of these agents with acute idiopathic neuropathy include possession of antigens shared with myelin and inhibition of suppressor mechanisms.At least half of the reported cases of Guillain-Barre syndrome (GBS) have been preceded by infections or other antecedent events during the few weeks before the neuropathy.' A large number of events have been incriminated and in one study of 1100 case records there were 735 possible associations.2 These include a variety of different infections, vaccinations, metabolic and neoplastic conditions. The only two case controlled studies suggested a higher incidence of respiratory infections3 and gastroenteritis4 among GBS patients than in appropriate controls. Serological tests have implicated cytomegalovirus (CMV) and Epstein Barr virus (EBV) more frequently than other viruses.

Summary Human papillomavirus (HPV) typing and quantitation by polymerase chain reaction was performed on exfoliated cells from 133 women referred for colposcopy because of an abnormal smear. High levels of HPV 16 correctly predicted cervical intraepithelial neoplasia (CIN) grade II-III in 93% of its occurrences, but only 59% of cases of CIN III were associated with high levels of this type. Eighty-four per cent of CIN III lesions contained high levels of at least one of HPV types 16, 18, 31, 33 and 35, but the other types were less specific for CIN III than HPV 16. Overall HPV testing compared favourably with cytology for predicting high-grade CIN lesions, but it would appear that some combination of the two modalities will produce better performance than either alone. In particular, HPV testing appears to be helpful in determining which women with mildly abnormal smears have high-grade underlying lesions in need of immediate referral for colposcopy.Cytological screening for cervical dysplasia is an effective method of reducing the incidence of and mortality from cervix cancer (Hakama, 1982; IARC Working Group, 1986;Laara et al., 1987;Hakama et al., 1991 (Barton et al., 1989;Szarewski et al., 1991). Possibly these can be safely left until the next routine smear, but invasive cancer can also be missed (Mitchell et al., 1990). Lastly, on the scale practised today, cytological examination of slides for dyskaryotic changes is a time-consuming, tedious and eye-fatiguing activity leading to difficulty in recruiting and keeping staff, and making the cost-effectiveness of the programme less favourable than it might be.In the past two decades much effort has been devoted towards trying to automate and simplify the preparation and reading of smears, and several prototype computer-assisted screening systems are under evaluation (Banda-Gamboa et al., 1992). However, none is currently in routine use, and interest in alternative or complementary modalities is high. The most thoroughly evaluated among these is cervicography (Stafl, 1981;Tawa et al., 1988;Szarewski et al., 1991), which is highly sensitive but does not appear to be sufficiently specific. However, the possibility that has stimulated the most interst is the detection and typing of HPV DNA in exfoliated cervical cells Schiffman et al., 1991;van den Brule et al., 1991;Koutsky et al., 1992 In this paper we extend that report by increasing the number of women studied and by looking individually at several HPV types. The specific aim was to examine the value of HPV typing for deciding which women with mild cervical abnormalities detected by cytology actually harbour a highgrade (CIN II/III) lesion and are in need of immediate referral for colposcopy. We also wished to examine the relative value of the different HPV types in predicing high-grade disease. The use of HPV DNA detection, typing and quantification in primary screening will not be addressed here and is the subject of several large ongoing studies. Patients and methodsPatients referred for colposcopy were stu...

Erythema infectiosum (EI) or fifth disease is a mild, acute exanthematous disease, occurring mainly among children, for which a causative virus has long been sought. In May 1983 an outbreak of exanthematous illness was reported in a primary school in North London. Children attending the school were investigated by questionnaire and 162 (43.9%) reported an illness with the features of EI. In each of 36 cases investigated virologically the illness was associated with parvovirus infection. Moreover, pre-existing antibody to parvovirus was correlated with protection from EI in 16 of 17 close family contacts of cases. We propose therefore that EI is the common manifestation of infection with the human parvovirus.

BackgroundThe presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied. Design and MethodsBy using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia. ResultsParoxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16 - CD66b-clones being larger than those of CD55 -CD59 -(p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging. ConclusionsThese results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD16/CD66b antibody combination is superior to CD55/CD59 in screening for subclinical paroxysmal nocturnal hemoglobinuria because it detects a large clone size and is less subject to analytical interference.

Infection of normal individuals with human parvovirus (B19) results in a mild disease (erythema infectiosum) but gives rise to aplastic crises in patients with chronic hemolytic anemias. The effects of this disease on hemopoiesis were investigated following intranasal inoculation of the virus into three volunteers. A typical disease ensued with a viremia peaking at 9 d. Marrow morphology 6 d after inoculation appeared normal but at 10 d there was a severe loss of erythroid precursors followed by a 1-2-g drop in hemoglobin, and an increase in serum immunoreactive erythropoietin. Erythroid burst-forming units (BFU-E) from the peripheral blood were considerably reduced, starting at the time of viremia and persisting for 4-8 d depending on the individual. Granulocyte-macrophage colony-forming units (CFU-GM) were also affected but the loss started 2 d later. Both CFU-GM and BFU-E showed a sharp overshoot at recovery. In the marrow, BFU-E and CFU-E were reduced at 6 and 10 d in the individual having the longest period of peripheral progenitor loss. In contrast, there was an increase in BFU-E and CFU-E in the subject with least change in peripheral progenitors. In the third subject, with an intermediate picture, there was a loss at 6 d but an increase at 10 d of erythroid progenitors. It is suggested that the architecture of the marrow might partially isolate progenitors from high titers of virus in the serum and individual variation in this respect might give the results observed.